Mutations　in　Kras　gene　may　be　used　as　a　diagnostic　marker　and　a　target　for　treatment　of　the　broad　spectrum　of　human　cancers.　In　this　study,　we　developed　a　new　class　of　amplification　assay,　double-hairpin　molecular　beacon　(DHMB)-based　cascade　rolling　circle　amplification　(RCA),　for　ultrasensitive　and　selective　detection　of　Kras　gene　in　a　homogenous　solution.　Specifically,　target　DNA　can　hybridize　with　DHMB　and　activate　cyclical　target　strand-displacement　polymerization　(CTDP)　and　nicking-mediated　strand-displacement　polymerization　(NMDP).　The　resulting　nicked/displaced　fragments　substantially　outnumber　target　DNA　and　cause　the　cascade　rolling　circle　amplification　(C-RCA)　and　nicked　fragment-induced　strand-displacement　polymerization　(NFDP).　Even　if　four　amplification　processes　are　designed,　only　DHMB,　padlock　probe　and　polymerization　primer　are　involved.　Under　optimized　conditions,　this　screening　system　exhibits　a　linear　range　of　5　orders　of　magnitude　(from　100　fM　to　20　nM),　and　the　detection　limit　is　down　to　16　fM.　Moreover,　the　developed　biosensing　system　offers　a　high　assay　specificity　for　perfectly　matched　target　DNA,　and　the　measured　data　from　practical　samples　demonstrated　the　potential　application　in　the　cancer　diagnoses.　As　a　proof-of-concept　genetic　assay,　the　novel　signaling　strategy,　as　well　as　desirable　analytical　capability,　would　significantly　benefit　the　development　of　versatile　amplification　gene　profiling　platforms,　revealing　great　promise　in　biological　studies　and　medical　diagnostics.　©　2016　Elsevier　B.V.